Conspectus on nanodiagnostics as an incipient platform for detection of oral potentially malignant disorders and oral squamous cell carcinoma
Authors: Dilip K. Shanmugam, Srinidhiy C. Anitha, Rizwan A. Najimudeen, Muthupandian Saravanan, Jesu Arockiaraj, Melaku A. Belete
Journal: International Journal of Surgery (2023)

One of the most common causes of death around the globe is cancer. One of the most prevalent forms of cancer is the cancer of the oral cavity and oropharynx known as oral squamous cell carcinoma (OSCC). The susceptivity to various viruses, smoking, overindulgence in tobacco, alcohol consumption, occupational exposure, increased sun exposure, and nutritional deficiencies resulting from low socioeconomic status are the preponderant risk factors which lead to genetic and epigenetic transmutation1,2. OSCC potentially spread quickly and the initial stage is referred to as the oral potentially malignant disorder (OPMD). The OPMD symptoms are white or red lesions in the mouth, paresthesia, trismus or jaw hypomobility gradually pronounce into severe vocal changes and oral ulcers which are basically nontreatable3. This illness has the potential to spread quickly, and it can frequently invade nearby tissues4. Since the OPMD indications were usually staved off, the OSCC becomes life-threatening and is thus associated with high morbidity rates. Hence, early detection of the very early OPMD stage is very critical in order to improve the health benefits of the patient and curb the prognosis of the disease. This article provides a brief summary of diagnostic strategies in the detection of oral cancer especially using nanotechnology, and the current trends and future prospects in nanodiagnostics. There are numerous tests available to diagnose oral and oropharyngeal cancer. Common techniques for diagnosing OSCC are endoscopy, oral brush biopsy, human papillomavirus testing, positron emission tomography scan, ultrasound, MRI, computed tomography, and radiography. Emerging detection techniques like nanodiagnostics provide advantages over the contrast agents used in modern imaging. Nanoparticles (NPs) will target specific surface molecules, are simpler to synthesize, and are more biocompatible than larger particles. Nanodiagnostics have exceptional characteristics like their size, high mechanical strength, shape, and surface. Nanomaterial-based sensors are significantly more sensitive than normal sensors. They also offer real-time tracking5, surface-enhanced Raman spectroscopy, MRI, optical coherence tomography, nano-based ultrasensitive biomarker detection, Quantum Dots (QDs) imaging, photoacoustic imaging, diffusion reflection imaging, and surface plasmon resonance scattering are some of the implementations of nano-based diagnostics6. The NPs currently used in oral cancer diagnosis are listed in Table 1. Table 1 - Nanoparticles for diagnosis of oral cancer Nanoparticles Description References Liposomes Liposomes are extensive in diagnostic research. Compared to 18F-FDG, 64Cu liposomes are more capable to recognize tumors in the early stage 7 Dendrimers The detection of oral malignancies can be done by an attractive device, Dendrimers. Wei et al. constructed DNA-dendrimer and poly-pyrrole (DDPpy) sensors for the detection of oral cancer biomarkers such as interleukin-1 protein, interleukin-8 RNA and interleukin-8 protein, which have improved specificity and greater bioaffinity 8 Gold NPs A noninvasive, efficient method for diagnosing OSCC is SERS 9 According to Xue and Wang's study, the SERS approach could be utilized to examine and distinguish between OSCC and even the various tumor stages. Gold NPs can greatly increase the SERS spectrum's intensities by adding to serum samples 10 For the electrochemical detection of oral cancer as an immunosensing platform, a customized AuNPs-rGO (gold-NP-reduced grapheneoxide) based bioelectrode has been designed 11 Magnetic NPs (MNPs) For MRI contrast agents, MNPs have been researched. They also assist in refining proton relaxation, then progressively developing as a contrast in both fields of biological and medical diagnostics with useful probes 12 MNPs can also be administered to the location of the tumor with precision, avoiding adjacent organs 13 Polymeric NPs Fluorescent endoscopic detection of oral cancer has been described by Yang et al. using Highly performing NPs. The folate receptors on oral cancer cells are targeted for nanoparticle endocytosis that is improved by Folic acid conjugated chitosan NPs. By reducing the interface between chitosan and the drug, the release of 5-aminolevulinic acid (5-ALA) in oral cancer cells can be boosted by the N-succinyl chitosan (SCHI) polymer with a negative charge 14 NP, nanoparticle; OSCC, oral squamous cell carcinoma; SERS, surface-enhanced Raman spectroscopy. Numerous developments have been made in the field of diagnostics as an outcome of the urgent need for sensitive, precise, strong, and quick diagnosis of oral cancer15,16. Recent developments in the field of nanotechnology offer the necessary incentive for nanobiosensor technology development17. Nanobiosensing techniques for OSCC detection are substrate selection, surface cleaning, surface enhancement by incorporation of NPs, surface enhancement by polymers, surface functionalization, biorecognition probe, and its immobilization (Fig. 1)18. In order to diagnose oral cancer, artificial intelligence is applied, such as the detection of precancerous as benign and postcancerous as malignant regions using automated deep learning CNN (Convolutional Neural Network) technique19. CNN is a deep learning algorithm. The major purpose of CNN is that it automatically identifies desired features and provide image recognition, with no human assistance. For the screening of oral cancer, deep CNNs can be a practical way to create low-cost embedded vision systems with constrained memory and processing power20. A significant advancement in recent years is the biosensor based on QDs that help with the diagnosis of some oral cancer biomarkers21. By conjugating QDs with complements of molecular biomarkers, multifunctional NP probes have been developed. QD probes can be often used to determine the molecular biomarker expression in oral cancer cells.Figure 1: Nanomaterial promising structures for the management of oral cancer.It is now evident that the NPs have demonstrated great promise and success in fundamentally altering the strategy for detecting oral cancer. Also, we sought to discuss key aspects of NP synthesis such as design criteria, cutting-edge experimental techniques, and NP platforms for OSCC diagnosis. The use of unique molecular markers will aid in the future development of active targeting magnetic NPs to significantly enhance tumor localization and diagnosis. Ethical approval Not applicable. Sources of funding None. Author contribution D.K.S.: investigation, writing – original draft preparation. S.C.A.: data collection, visualization, and original draft preparation. R.A.N.: investigation and data curation. M.S.: conceptualization, writing – reviewing and editing and supervision. J.A.: investigation, writing – reviewing and editing and supervision. M.A.B.: conceptualization, writing – reviewing and editing and supervision. Conflicts of interest disclosure The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Research registration unique identifying number (UIN) None. Guarantor Melaku Ashagrie Belete. Data statement All data are available in the manuscript.